{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T15:32:21Z","timestamp":1770910341439,"version":"3.50.1"},"reference-count":32,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"unspecified","delay-in-days":18,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dutch Organization for Health Research and Health Care Innovation","award":["10140022110039"],"award-info":[{"award-number":["10140022110039"]}]},{"name":"Besins Healthcare"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,10,22]]},"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Couples diagnosed with unexplained subfertility are advised to start mild ovarian hyperstimulation and intrauterine insemination (MOH-IUI) as a primary treatment. Natural feedback mechanisms and hormone release are affected by artificially stimulated cycles and induced ovulation. Additional luteal support could positively affect progesterone patterns in the luteal phase. The LUMO study evaluates whether the addition of exogenous progesterone in the luteal phase following MOH-IUI treatment cycle will improve pregnancy and live birth rates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>A multicentre randomised, double-blind, controlled trial will be conducted in Dutch fertility clinics, academic and non-academic hospitals. There are two treatment arms: group A progesterone luteal phase support; group B placebo, without crossover. All initiated MOH-IUI cycles within 6 months after randomisation are included (study period). Participants will start study medication, applying a daily dosage of 2dd 300\u2009mg progesterone (Utrogestan) or 2dd 300\u2009mg placebo in vaginal capsules on the second day after the IUI procedure. Treatment is continued until the onset of menstruation, a negative pregnancy test (IUI+14 days), a miscarriage or until 7\u2009weeks of gestation in case of a viable pregnancy. Follow-up ends at 12 months after the end of study period (18 months after study randomisation). The primary outcome is cumulative pregnancy rate, achieved within 6\u2009months after randomisation, leading to live birth. A total of 1008 patients (504 patients in each group) will be included.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The study was approved by the Central Committee on Research Involving Human Subjects on 30 January 2023. All participating sites have the approval of the local Board of Directors to participate in the LUMO study. An informed consent form will be signed by all participants. Study results will be presented at (inter)national conferences and published in peer-reviewed journals. It is expected that the results of this trial will be used to draft national guidelines on this issue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      The study is registered in the EU CTIS trial register (2022-501534-33-00), the Dutch trial registry (registration number: LTR 24508), ClinicalTrials.gov (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05080569\">NCT05080569<\/jats:ext-link>\n                      ) and the WHO registry (universal trial number: U1111-1280-9461).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-111872","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T08:52:23Z","timestamp":1763628743000},"page":"e111872","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Does luteal phase support in MOH-IUI treatment improve cumulative live birth rates in couples with unexplained subfertility? Study protocol of the LUMO study: a multicentre, randomised, double-blind, controlled trial with cost-effectiveness analysis"],"prefix":"10.1136","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct05080569","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05080569","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0248-0688","authenticated-orcid":false,"given":"Emma","family":"Preesman","sequence":"first","affiliation":[{"name":"Division Woman and Baby, University Medical Centre Utrecht, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja","family":"Drechsel","sequence":"additional","affiliation":[{"name":"Division Woman and Baby, University Medical Centre Utrecht, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heleen","family":"Crommelin","sequence":"additional","affiliation":[{"name":"Laboratories, Pharmacy, and Biomedical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Broekmans","sequence":"additional","affiliation":[{"name":"Division Woman and Baby, University Medical Centre Utrecht, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willem","family":"Verpoest","sequence":"additional","affiliation":[{"name":"Division Woman and Baby, University Medical Centre Utrecht, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Broer","sequence":"additional","affiliation":[{"name":"Division Woman and Baby, University Medical Centre Utrecht, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"2026021203300675000_15.11.e111872.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0378(01)00134-6"},{"key":"2026021203300675000_15.11.e111872.2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(72)90181-0"},{"key":"2026021203300675000_15.11.e111872.3","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/"},{"key":"2026021203300675000_15.11.e111872.4","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.rbmo.2013.06.010","article-title":"Oestrogen and progesterone action on endometrium: a translational approach to understanding endometrial receptivity","volume":"27","author":"Young","year":"2013","journal-title":"Reprod Biomed"},{"key":"2026021203300675000_15.11.e111872.5","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1093\/humrep\/14.suppl_2.107","article-title":"Ovarian stimulation and endometrial receptivity","volume":"14 Suppl 2","author":"Valbuena","year":"1999","journal-title":"Hum Reprod"},{"key":"2026021203300675000_15.11.e111872.6","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/S0015-0282(16)46636-7","article-title":"Morphometric analysis of the human endometrium in relation to peripheral hormone levels","volume":"38","author":"Johannisson","year":"1982","journal-title":"Fertil Steril"},{"key":"2026021203300675000_15.11.e111872.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.07.027"},{"key":"2026021203300675000_15.11.e111872.8","doi-asserted-by":"publisher","DOI":"10.1210\/er.18.4.502"},{"key":"2026021203300675000_15.11.e111872.9","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dml020"},{"key":"2026021203300675000_15.11.e111872.10","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(03)00075-4"},{"key":"2026021203300675000_15.11.e111872.11","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/16.4.663"},{"key":"2026021203300675000_15.11.e111872.12","first-page":"51","article-title":"The effect of luteal phase support on pregnancy rates of the stimulated intrauterine insemination cycles in couples with unexplained infertility","volume":"4","author":"Ebrahimi","year":"2010","journal-title":"Int J Fertil Steril"},{"key":"2026021203300675000_15.11.e111872.13","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1210\/jc.2018-00642","article-title":"Midluteal Progesterone: A Marker of Treatment Outcomes in Couples With Unexplained Infertility","volume":"103","author":"Hansen","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"2026021203300675000_15.11.e111872.14","article-title":"Intra-uterine insemination for unexplained subfertility","volume":"3","author":"Ayeleke","year":"2020","journal-title":"Cochrane Database Syst Rev"},{"key":"2026021203300675000_15.11.e111872.15","unstructured":"Nederlandse Zorgautoriteit . 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